WO1995028925A1 - Moyen prophylactique/remede contre certaines maladies - Google Patents

Moyen prophylactique/remede contre certaines maladies Download PDF

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Publication number
WO1995028925A1
WO1995028925A1 PCT/JP1995/000848 JP9500848W WO9528925A1 WO 1995028925 A1 WO1995028925 A1 WO 1995028925A1 JP 9500848 W JP9500848 W JP 9500848W WO 9528925 A1 WO9528925 A1 WO 9528925A1
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WO
WIPO (PCT)
Prior art keywords
cells
ascorbic acid
preventing
apoptosis
unnecessary
Prior art date
Application number
PCT/JP1995/000848
Other languages
English (en)
Japanese (ja)
Inventor
Seiichi Tanuma
Original Assignee
Seiichi Tanuma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Seiichi Tanuma filed Critical Seiichi Tanuma
Priority to US08/765,298 priority Critical patent/US5955498A/en
Publication of WO1995028925A1 publication Critical patent/WO1995028925A1/fr
Priority to US09/186,408 priority patent/US6306901B1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof

Definitions

  • the present invention relates to a medicament for preventing and / or treating a disease caused by unnecessary or pathogenic cells, comprising ascorbic acid or the like as an active ingredient, a method for preventing and / or treating the disease, and a method for preventing and / or treating the disease. And / or use of ascorbic acid or the like for the manufacture of a medicament for treatment.
  • apoptosis which means active cell death programmed in a gene and is also referred to as cell self-death, self-death, or apobutosis.
  • This apoptosis unlike necrosis, which is pathological cell death, is thought to be death that is integrated into the cell's own genes from the beginning.
  • some external or internal factors trigger the apoptosis-programming gene, which activates the apoptosis protein that is biosynthesized based on this gene or the existing apoptotic protein. It is thought that the cells themselves are actively destroyed by this, leading to death.
  • the present inventors have conducted intensive studies to develop a novel drug having an apoptosis-inducing effect, and as a result, ascorbic acid and its derivatives, and their salts (hereinafter collectively referred to as “ Have a selective apoptosis-inducing effect on unwanted or pathogenic cells and are useful for the prevention and / or treatment of diseases caused by such cells. That is, the present invention is as follows.
  • Ascorbic acid used in the present invention is a known compound.
  • the derivative include benzylidene-ascorbic acid.
  • Benzylidenascorbic acid is also a known compound, and specifically, 5,6-0-benzylidene-L-ascorbic acid and the like represented by the following formula are exemplified. (Steroids) J. 12, p309 (1968).
  • ascorbic acid include acylated forms of the hydroxyl group at the 6-position of ascorbic acid [Japanese Patent Application Laid-Open No. Sho 60-410103 (WPI Acc NO: 85-046633 / 08), Expl. Cell Biol., 54. p245 (86), vitamins, 61, pl99 (87), etc.], ethylidene and pentadecylidene in which the 5- and 6-position hydroxyl groups are integrated [JP-A-58-13] 197 8 publication (refer to US Pat. No. 4,552,888, GB2114571)) and benzylidene form [see Japanese Patent Application Laid-Open No. Hei 11-313476 (WPI Acc NO: 90-034400 / 05)] .
  • 6-propionylascorbic acid 6-octanoylascorbic acid, 6-palmitoylascorbic acid, 6-benzoylascorbic acid, 5, 6-0— 1-methylethylidene) ascorbic acid, 5, 6—0— (1 benzene) Roux 2-phenylenylidene) ascorbic acid, 5, 6-0- pentadecylidene-completed scorbic acid, and 5,6-0- ⁇ -ditrobenzylidene-ascorbic acid.
  • Methods for preparing these derivatives are disclosed in each of the above references.
  • the ascorbic acids contained in the agent for preventing and treating diseases of the present invention have low toxicity and have an apoptosis-inducing action that is unnecessary or selective for pathogenic cells. Or it is useful for treatment.
  • it is useful as an anticancer agent, an anti-cancer agent, or for the prevention and / or treatment of many diseases caused by various viral infections.
  • it has an apoptosis-inducing effect on unwanted or pathogenic cells, so it is useful for the prevention and / or treatment of infection by the HIV virus, and for the prevention and / or treatment of acquired immunodeficiency syndrome (AIDS).
  • AIDS acquired immunodeficiency syndrome
  • the agent for preventing or treating a disease of the present invention is provided in the form of a solid preparation, a semi-solid preparation and a liquid preparation containing an organic or inorganic carrier and / or an excipient suitable for external use, oral administration or topical administration.
  • the prophylactic / therapeutic agent of the present invention, together with pharmacologically acceptable auxiliary components includes, for example, powders, granules, tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions, injections, syrups It is used to provide a suitable dosage form such as a preparation, an external preparation and the like.
  • auxiliary ingredients include solids such as, for example, water, glucose, lactose, gelatin, mannitol, starch paste, magnesium trigeate, corn starch, keratin, colloidal silica, potato starch, urea, etc. Includes those that can be used effectively in the manufacture of semisolid or liquid formulations.
  • auxiliary substances such as stabilizers, fillers, coloring agents and fragrances can be included.
  • ascorbin Preservatives can be included to retain the activity of the acids, and should contain a sufficient amount of ascorbic acid to produce the desired therapeutic effect on the progress or condition of the associated disease. is there.
  • an effective amount of ascorbic acid is desirably administered nonperiodically, for example, by injection, or orally.
  • the dosage of the agent for preventing or treating a disease of the present invention varies depending on gender, age, body weight, symptoms, therapeutic effect, administration method, administration period, and the like.For example, about 100 to 300 mgZ days for an adult patient is preferred. Is exemplified.
  • U933 cells human monocyte blast-like cells
  • TPA phorbol ester
  • TNF tumor necrosis factor
  • HL-60 human promyelocytic leukemia cells
  • Lympho normal human lymphocytes
  • the percentage of cells that induced apoptosis after treating each cell for 6 hours in the presence of SBA was calculated by measuring DNA fragmentation according to Experimental Example 1. The results are shown in Table 2 below.
  • SBA induced apoptosis in tumor cells, HL-60 cells, in a g-degree-dependent manner.
  • normal human lymphocytes did not induce apoptosis at the same g-degree, indicating that the apoptosis-inducing effect of SBA is selective for tumor cells.
  • SBA had no effect on normal human lymphocytes up to 3 OmM, indicating that cytotoxicity was sufficiently low.
  • Ascorbic acid induced apoptosis in HL-60 cells, which are tumor-tolerant cells, in a concentration-dependent manner.
  • normal human lymphocytes did not induce apoptosis at the same concentration, indicating that apoptosis-inducing action of ascorbic acid has selectivity for tumor cells.
  • ascorbic acid had no effect on normal human lymphocytes up to 1 OmM, indicating that the cytotoxicity was sufficiently low.
  • the mixed powder was beaten to give a tablet of 20 mg per tablet.
  • the tablet may be coated, if necessary, with a commonly used gastrosoluble film coating agent (for example, polyvinylacetal dimethylaminoacetate) or an edible colorant.
  • a commonly used gastrosoluble film coating agent for example, polyvinylacetal dimethylaminoacetate
  • the above components were uniformly mixed, and the mixed powder was filled with 20 mg of hard gelatin capsule.
  • Ascorbic acids contained in the agent for preventing and treating diseases of the present invention have low toxicity, and furthermore, have an unnecessary or selective apoptosis-inducing effect on pathogenic cells, and thus prevent and / or prevent diseases caused by the cells.
  • Useful for treatment For example, it is useful as an anticancer drug, an anticancer drug, or for the prevention and / or treatment of many diseases caused by various viral infections. In particular, since it has an apoptosis-inducing effect on unwanted or pathogenic cells, it is useful for the prevention and / or treatment of infection by the HIV virus and the prevention and / or treatment of acquired immunodeficiency syndrome (AIDS). Useful.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention se rapporte à un médicament contenant de l'acide ascorbique, à un dérivé de celui-ci, ou à un sel de l'acide ou du dérivé (désigné ci-après sous le nom d'ascorbate en géneral) utilisé comme ingrédient actif en vue d'induire sélectivement l'apoptose de cellules inutiles ou pathogènes afin de prévenir et/ou guérir les maladies provoquées par ces cellules; à un procédé visant à prévenir et/ou guérir les maladies provoquées par des cellules inutiles ou pathogènes au moyen de l'ascorbate afin d'induire sélectivement l'apoptose de ces cellules; et à l'utilisation de l'ascorbate pour obtenir un médicament qui sera utilisé pour induire sélectivement l'apoptose de cellules inutiles ou pahtogènes afin de prévenir et/ou guérir les maladies provoquées par ces cellules. Du fait que l'ascorbate est légèrement toxique et a l'effet d'induire sélectivement l'apoptose des cellules inutiles ou pathogènes, il est utilisé pour prévenir et/ou guérir les maladies provoquées par ces cellules. Par exemple, il est utilisé comme agent cancérostatique, comme médicament anticancéreux, et dans la prophylaxie et/ou la thérapie de maladies provoquées par des infections virales. Il est notamment utilisé pour prévenir et/ou guérir les infections dues au VIH et le SIDA.
PCT/JP1995/000848 1994-04-27 1995-04-27 Moyen prophylactique/remede contre certaines maladies WO1995028925A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US08/765,298 US5955498A (en) 1994-04-27 1995-04-27 Agent for prophylaxis and therapy of diseases
US09/186,408 US6306901B1 (en) 1994-04-27 1998-11-05 Agent for prophylaxis and therapy of diseases

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP6/90372 1994-04-27
JP9037294 1994-04-27
JP10707994 1994-05-20
JP6/107079 1994-05-20

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US08/765,298 Continuation-In-Part US5955498A (en) 1994-04-27 1995-04-27 Agent for prophylaxis and therapy of diseases

Publications (1)

Publication Number Publication Date
WO1995028925A1 true WO1995028925A1 (fr) 1995-11-02

Family

ID=26431861

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1995/000848 WO1995028925A1 (fr) 1994-04-27 1995-04-27 Moyen prophylactique/remede contre certaines maladies

Country Status (3)

Country Link
US (2) US5955498A (fr)
CA (1) CA2193838A1 (fr)
WO (1) WO1995028925A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0765662A1 (fr) * 1994-06-20 1997-04-02 Mutsuyuki Kochi Composition inhibitrice de la croissance du virus vih
WO2003032979A1 (fr) * 2001-10-10 2003-04-24 Mutsuyuki Kochi Compositions induisant une differenciation de cellules malignes et leur utilisation

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064245A1 (fr) * 2000-02-29 2001-09-07 Showa Denko K.K. Composition de renforcement immunitaire et utilisation de ces compositions
CA2556437A1 (fr) * 2004-02-20 2005-09-09 Robert F. Hofmann Utilisation d'une formulation therapeutique oxydative ciblee pour traiter des maladies virales

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60139619A (ja) * 1983-12-27 1985-07-24 Mutsuyuki Kochi Ｏ−ベンジリデン−アスコルビン酸又はその塩よりなる抗腫瘍剤
GB8810173D0 (en) * 1988-04-29 1988-06-02 Norsk Hydro As Pharmaceutical compositions with anti-cancer activity & method for treatment of cancer
US5135948A (en) * 1988-11-21 1992-08-04 Norsk Hydro A.S. Pharmaceutical compositions with anti-cancer activity against carcinoma and method for the treatment of carcinoma
GB9116030D0 (en) * 1991-07-25 1991-09-11 Ssali Charles L Antiviral compositions
JP2990015B2 (ja) * 1994-06-20 1999-12-13 睦之 東風 抗ｈｉｖ剤

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ANTICANCER RES., 13(1), 65-71 (1993). *
BIOCHEM. BIOPHYS. RES. COMMUN., 194(1), 29-35 (1993). *
FEBS LETT., 351(1), 105-8 (1994), 29 August 1994. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0765662A1 (fr) * 1994-06-20 1997-04-02 Mutsuyuki Kochi Composition inhibitrice de la croissance du virus vih
EP0765662A4 (fr) * 1994-06-20 1999-12-29 Mutsuyuki Kochi Composition inhibitrice de la croissance du virus vih
WO2003032979A1 (fr) * 2001-10-10 2003-04-24 Mutsuyuki Kochi Compositions induisant une differenciation de cellules malignes et leur utilisation

Also Published As

Publication number Publication date
US6306901B1 (en) 2001-10-23
US5955498A (en) 1999-09-21
CA2193838A1 (fr) 1995-11-02

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